Trial Outcomes & Findings for A Trial to Determine the Safety and Anti-tumor Activity Profile of the Combination of Cetuximab and Concomitant Cisplatin Plus 5-Fluorouracil (5-FU) in Subjects With Recurrent and/or Metastatic Squamous Cell Carcinoma in Head and Neck (NCT NCT01177956)

Last Updated: 2014-09-03

Results Overview

BOR: Percentage of participants experiencing a Complete Response (CR) (complete disappearance of measurable and evaluable disease without new lesions) or Partial Response (PR) (greater than or equal to 50 percent decrease of sum of product diameters of measurable disease, evaluable disease not worsening or progressing, no new lesions confirmed by a subsequent assessment no less than 28 days after criteria for response were first met) (based on modified World Health Organization \[WHO\] criteria), divided by the number of participants belonging to intention to treat (ITT) or safety population.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

73 participants

Primary outcome timeframe

Evaluations were performed every 6 weeks until progression, reported between day of first participant randomized, 25 December 2009, until cut-off date 25 January 2011

Results posted on

2014-09-03

Participant Flow

First/last participant (informed consent): December 2009/September 2010. Clinical data cut-off: 25 January 2011, Study completion date: November 2012

A total of 73 participants were enrolled, out of which 5 participants were screen failure and 68 participants received the study treatment.

Participant milestones

Participant milestones
Measure	Cetuximab + Cisplatin + 5-FU Participants were administered an initial dose of cetuximab 400 milligram per square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes followed by subsequent weekly doses of 250 mg/m\^2 IV infusion over 60 minutes along with background chemotherapy consisting of cisplatin 75 mg/m\^2 IV infusion over 60 minutes on day 1 of each 3-week treatment cycle and 5-fluorouracil (5-FU) 750 mg/m\^2 per day as a continuous IV infusion over 24 hours from day 1 to day 5 of each 3-week treatment cycle, for up to 6 cycles in the absence of progressive disease (PD) or unacceptable toxicity.
Overall Study STARTED	68
Overall Study COMPLETED	68
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Trial to Determine the Safety and Anti-tumor Activity Profile of the Combination of Cetuximab and Concomitant Cisplatin Plus 5-Fluorouracil (5-FU) in Subjects With Recurrent and/or Metastatic Squamous Cell Carcinoma in Head and Neck

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cetuximab + Cisplatin + 5-FU n=68 Participants Participants were administered an initial dose of cetuximab 400 milligram per square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes followed by subsequent weekly doses of 250 mg/m\^2 IV infusion over 60 minutes along with background chemotherapy consisting of cisplatin 75 mg/m\^2 IV infusion over 60 minutes on day 1 of each 3-week treatment cycle and 5-fluorouracil (5-FU) 750 mg/m\^2 per day as a continuous IV infusion over 24 hours from day 1 to day 5 of each 3-week treatment cycle, for up to 6 cycles in the absence of progressive disease (PD) or unacceptable toxicity.
Age, Continuous	55.7 years STANDARD_DEVIATION 9.5 • n=5 Participants
Age, Customized <65 years	55 participants n=5 Participants
Age, Customized >=65 years	13 participants n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants
Sex: Female, Male Male	49 Participants n=5 Participants
Race/Ethnicity, Customized Asian (Chinese)	63 participants n=5 Participants
Race/Ethnicity, Customized Asian (Korean)	5 participants n=5 Participants

PRIMARY outcome

Timeframe: Evaluations were performed every 6 weeks until progression, reported between day of first participant randomized, 25 December 2009, until cut-off date 25 January 2011

Population: ITT population included all participants who received at least one dose of the IMP cetuximab or chemotherapy.

Outcome measures

Outcome measures
Measure	Cetuximab + Cisplatin + 5-FU n=68 Participants Participants were administered an initial dose of cetuximab 400 milligram per square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes followed by subsequent weekly doses of 250 mg/m\^2 IV infusion over 60 minutes along with background chemotherapy consisting of cisplatin 75 mg/m\^2 IV infusion over 60 minutes on day 1 of each 3-week treatment cycle and 5-fluorouracil (5-FU) 750 mg/m\^2 per day as a continuous IV infusion over 24 hours from day 1 to day 5 of each 3-week treatment cycle, for up to 6 cycles in the absence of progressive disease (PD) or unacceptable toxicity.
Best Overall Response (BOR) Until Cut-off Date 25 January 2011	54.4 percentage of participants Interval 41.9 to 66.5

PRIMARY outcome

Timeframe: Evaluations were performed every 6 weeks until progression, reported between day of first participant randomized, 25 December 2009, until cut-off date 15 November 2012

Population: ITT population included all participants who received at least one dose of the investigational medicinal product (IMP) cetuximab or chemotherapy.

BOR: Percentage of participants experiencing a CR (complete disappearance of measurable and evaluable disease without new lesions) or PR (greater than or equal to 50 percent decrease of sum of product diameters of measurable disease, evaluable disease not worsening or progressing, no new lesions confirmed by a subsequent assessment no less than 28 days after criteria for response were first met) (based on modified WHO criteria), divided by the number of participants belonging to ITT or safety population.

Outcome measures

Outcome measures
Measure	Cetuximab + Cisplatin + 5-FU n=68 Participants Participants were administered an initial dose of cetuximab 400 milligram per square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes followed by subsequent weekly doses of 250 mg/m\^2 IV infusion over 60 minutes along with background chemotherapy consisting of cisplatin 75 mg/m\^2 IV infusion over 60 minutes on day 1 of each 3-week treatment cycle and 5-fluorouracil (5-FU) 750 mg/m\^2 per day as a continuous IV infusion over 24 hours from day 1 to day 5 of each 3-week treatment cycle, for up to 6 cycles in the absence of progressive disease (PD) or unacceptable toxicity.
Best Overall Response (BOR) Until Cut-off Date 15 November 2012	55.9 percentage of participants Interval 43.3 to 67.9

SECONDARY outcome

Timeframe: Time from randomization to death or last day known to be alive, reported between day of first participant randomized, 25 December 2009, until cut-off date 15 November 2012

Population: ITT population included all participants who received at least one dose of the IMP cetuximab or chemotherapy.

The OS time was defined as the time from first administration of trial treatment to death. Participants without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier.

Outcome measures

Outcome measures
Measure	Cetuximab + Cisplatin + 5-FU n=68 Participants Participants were administered an initial dose of cetuximab 400 milligram per square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes followed by subsequent weekly doses of 250 mg/m\^2 IV infusion over 60 minutes along with background chemotherapy consisting of cisplatin 75 mg/m\^2 IV infusion over 60 minutes on day 1 of each 3-week treatment cycle and 5-fluorouracil (5-FU) 750 mg/m\^2 per day as a continuous IV infusion over 24 hours from day 1 to day 5 of each 3-week treatment cycle, for up to 6 cycles in the absence of progressive disease (PD) or unacceptable toxicity.
Overall Survival (OS) Time Until Cut-off Date 15 November 2012	12.6 months Interval 9.1 to 15.0

SECONDARY outcome

Timeframe: Evaluations were performed every 6 weeks until progression, reported between day of first participant randomized, 25 December 2009, until cut-off date 25 January 2011

Population: ITT population included all participants who received at least one dose of the IMP cetuximab or chemotherapy.

Duration from first administration of trial treatment until progression (radiological or clinical, if radiological progression is not available) or death due to any cause. Only deaths within 60 days of last tumor assessment are considered. Participants without event are censored on the date of last tumor assessment.

Outcome measures

Outcome measures
Measure	Cetuximab + Cisplatin + 5-FU n=68 Participants Participants were administered an initial dose of cetuximab 400 milligram per square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes followed by subsequent weekly doses of 250 mg/m\^2 IV infusion over 60 minutes along with background chemotherapy consisting of cisplatin 75 mg/m\^2 IV infusion over 60 minutes on day 1 of each 3-week treatment cycle and 5-fluorouracil (5-FU) 750 mg/m\^2 per day as a continuous IV infusion over 24 hours from day 1 to day 5 of each 3-week treatment cycle, for up to 6 cycles in the absence of progressive disease (PD) or unacceptable toxicity.
Progression-free Survival (PFS) Time Until Cut-off Date 25 January 2011	6.2 months Interval 5.1 to 8.1

SECONDARY outcome

Timeframe: Evaluations were performed every 6 weeks until progression, reported between day of first participant randomized, 25 December 2009, until cut-off date 15 November 2012

Population: ITT population included all participants who received at least one dose of the IMP cetuximab or chemotherapy.

Outcome measures

Outcome measures
Measure	Cetuximab + Cisplatin + 5-FU n=68 Participants Participants were administered an initial dose of cetuximab 400 milligram per square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes followed by subsequent weekly doses of 250 mg/m\^2 IV infusion over 60 minutes along with background chemotherapy consisting of cisplatin 75 mg/m\^2 IV infusion over 60 minutes on day 1 of each 3-week treatment cycle and 5-fluorouracil (5-FU) 750 mg/m\^2 per day as a continuous IV infusion over 24 hours from day 1 to day 5 of each 3-week treatment cycle, for up to 6 cycles in the absence of progressive disease (PD) or unacceptable toxicity.
Progression-free Survival (PFS) Time Until Cut-off Date 15 November 2012	6.6 months Interval 5.1 to 7.7

SECONDARY outcome

Timeframe: Evaluations were performed every 6 weeks until progression, reported between day of first participant randomized, 25 December 2009, until cut-off date 25 January 2011

Population: ITT population included all participants who received at least one dose of the IMP cetuximab or chemotherapy.

Time from first administration of trial treatment to disease progression (radiological or clinical, if radiological progression is not available). Participants without event are censored on the date of last tumor assessment.

Outcome measures

Outcome measures
Measure	Cetuximab + Cisplatin + 5-FU n=68 Participants Participants were administered an initial dose of cetuximab 400 milligram per square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes followed by subsequent weekly doses of 250 mg/m\^2 IV infusion over 60 minutes along with background chemotherapy consisting of cisplatin 75 mg/m\^2 IV infusion over 60 minutes on day 1 of each 3-week treatment cycle and 5-fluorouracil (5-FU) 750 mg/m\^2 per day as a continuous IV infusion over 24 hours from day 1 to day 5 of each 3-week treatment cycle, for up to 6 cycles in the absence of progressive disease (PD) or unacceptable toxicity.
Time to Progression (TTP) Until Cut-off Date 25 January 2011	6.8 months Interval 5.3 to 8.1

SECONDARY outcome

Timeframe: Evaluations were performed every 6 weeks until progression, reported between day of first participant randomized, 25 December 2009, until cut-off date 15 November 2012

Population: ITT population included all participants who received at least one dose of the IMP cetuximab or chemotherapy.

Outcome measures

Outcome measures
Measure	Cetuximab + Cisplatin + 5-FU n=68 Participants Participants were administered an initial dose of cetuximab 400 milligram per square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes followed by subsequent weekly doses of 250 mg/m\^2 IV infusion over 60 minutes along with background chemotherapy consisting of cisplatin 75 mg/m\^2 IV infusion over 60 minutes on day 1 of each 3-week treatment cycle and 5-fluorouracil (5-FU) 750 mg/m\^2 per day as a continuous IV infusion over 24 hours from day 1 to day 5 of each 3-week treatment cycle, for up to 6 cycles in the absence of progressive disease (PD) or unacceptable toxicity.
Time to Progression (TTP) Until Cut-off Date 15 November 2012	7.0 months Interval 5.6 to 8.1

SECONDARY outcome

Timeframe: Evaluations were performed every 6 weeks until progression, reported between day of first participant randomized, 25 December 2009, until cut-off date 25 January 2011

Population: Subgroup of participants from the study population having best confirmed response (CR or PR).

Time from first assessment of CR or PR to disease progression or death (within 60 days of last tumor assessment). Participants without event are censored on the date of last tumor assessment. Tumor assessments based on modified WHO criteria.

Outcome measures

Outcome measures
Measure	Cetuximab + Cisplatin + 5-FU n=37 Participants Participants were administered an initial dose of cetuximab 400 milligram per square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes followed by subsequent weekly doses of 250 mg/m\^2 IV infusion over 60 minutes along with background chemotherapy consisting of cisplatin 75 mg/m\^2 IV infusion over 60 minutes on day 1 of each 3-week treatment cycle and 5-fluorouracil (5-FU) 750 mg/m\^2 per day as a continuous IV infusion over 24 hours from day 1 to day 5 of each 3-week treatment cycle, for up to 6 cycles in the absence of progressive disease (PD) or unacceptable toxicity.
Duration of Response Until Cut-off Date 25 January 2011	5.7 months Interval 4.2 to 9.1

SECONDARY outcome

Timeframe: Evaluations were performed every 6 weeks until progression, reported between day of first participant randomized, 25 December 2009, until cut-off date 15 November 2012

Population: Subgroup of participants from the study population having best confirmed response (CR or PR).

Outcome measures

Outcome measures
Measure	Cetuximab + Cisplatin + 5-FU n=38 Participants Participants were administered an initial dose of cetuximab 400 milligram per square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes followed by subsequent weekly doses of 250 mg/m\^2 IV infusion over 60 minutes along with background chemotherapy consisting of cisplatin 75 mg/m\^2 IV infusion over 60 minutes on day 1 of each 3-week treatment cycle and 5-fluorouracil (5-FU) 750 mg/m\^2 per day as a continuous IV infusion over 24 hours from day 1 to day 5 of each 3-week treatment cycle, for up to 6 cycles in the absence of progressive disease (PD) or unacceptable toxicity.
Duration of Response Until Cut-off Date 15 November 2012	6.1 months Interval 5.4 to 7.8

Adverse Events

Cetuximab + Cisplatin + 5-FU : Treatment Emergent Phase

Serious events: 13 serious events

Other events: 67 other events

Deaths: 0 deaths

Cetuximab + Cisplatin + 5-FU : Late Phase

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Merck KGaA Communication Center

Merck Serono, a division of Merck KGaA

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee All submissions by the PI for publication require the written permission from the sponsor. The PI commits to forward to the sponsor all documents intended for publication which contains data or results generated in connection with the study. Documents must be available at least 60 days before the planned submission date to allow for review. Any publication should follow the policy in the protocol. The PI shall not publish results derived from the study until the study has been reported in full.
Publication restrictions are in place

Restriction type: OTHER

Measure	Cetuximab + Cisplatin + 5-FU : Treatment Emergent Phase n=68 participants at risk Participants were administered an initial dose of cetuximab 400 milligram per square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes followed by subsequent weekly doses of 250 mg/m\^2 IV infusion over 60 minutes along with background chemotherapy consisting of cisplatin 75 mg/m\^2 IV infusion over 60 minutes on day 1 of each 3-week treatment cycle and 5-fluorouracil (5-FU) 750 mg/m\^2 per day as a continuous IV infusion over 24 hours from day 1 to day 5 of each 3-week treatment cycle, for up to 6 cycles in the absence of progressive disease (PD) or unacceptable toxicity. On or after the first dosing day of trial treatment and until 30 days after the last trial treatment administration.	Cetuximab + Cisplatin + 5-FU : Late Phase n=32 participants at risk Participants were administered an initial dose of cetuximab 400 milligram per square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes followed by subsequent weekly doses of 250 mg/m\^2 IV infusion over 60 minutes along with background chemotherapy consisting of cisplatin 75 mg/m\^2 IV infusion over 60 minutes on day 1 of each 3-week treatment cycle and 5-fluorouracil (5-FU) 750 mg/m\^2 per day as a continuous IV infusion over 24 hours from day 1 to day 5 of each 3-week treatment cycle, for up to 6 cycles in the absence of progressive disease (PD) or unacceptable toxicity. Participants with end of treatment date after the last trial treatment date + 30 days or still on trial at the cut-off date.
Immune system disorders Anaphylactic reaction	2.9% 2/68 • Number of events 3 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.	0.00% 0/32 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.
Blood and lymphatic system disorders Microcytic anemia	1.5% 1/68 • Number of events 1 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.	0.00% 0/32 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.
Cardiac disorders Myocardial infarction	1.5% 1/68 • Number of events 1 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.	0.00% 0/32 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.
Gastrointestinal disorders Mouth hemorrhage	1.5% 1/68 • Number of events 1 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.	0.00% 0/32 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.
General disorders Pyrexia	1.5% 1/68 • Number of events 1 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.	0.00% 0/32 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.
Infections and infestations Pneumonia	1.5% 1/68 • Number of events 1 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.	0.00% 0/32 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.
Infections and infestations Staphylococcal skin infection	1.5% 1/68 • Number of events 1 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.	0.00% 0/32 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.
Metabolism and nutrition disorders Electrolyte imbalance	1.5% 1/68 • Number of events 1 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.	0.00% 0/32 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.
Metabolism and nutrition disorders Hypomagnesaemia	1.5% 1/68 • Number of events 1 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.	0.00% 0/32 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor hemorrhage	1.5% 1/68 • Number of events 1 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.	0.00% 0/32 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.
Nervous system disorders Toxic encephalopathy	1.5% 1/68 • Number of events 1 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.	0.00% 0/32 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.5% 1/68 • Number of events 1 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.	0.00% 0/32 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.5% 1/68 • Number of events 1 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.	0.00% 0/32 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.
Respiratory, thoracic and mediastinal disorders Respiratory alkalosis	1.5% 1/68 • Number of events 1 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.	0.00% 0/32 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.
Vascular disorders Venous thrombosis	1.5% 1/68 • Number of events 1 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.	0.00% 0/32 • Baseline until 30 days after last trial treatment An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP regardless of causal relationship and even if no IMP has been administered.